Antitumor efficacy induced by human ovarian cancer cells secreting IL-21 alone or combination with GM-CSF cytokines in nude mice model

作者：Dou Jun^*; Wang Yongfang; Wang Jing; Zhao Fengshu; Li Yating; Cao Minggang; Hu Weihua; Hu Kai; He Xiang Feng; Chu Lili; Jiang Chuilian; Gu Ning

来源：Immunobiology, 2009, 214(6): 483-492.

DOI：10.1016/j.imbio.2008.11.002

• Ovarian cancer
• Antitumor
• IL-21
• GM-CSF
• Gene transfection
• Nude mouse

The ovarian cancer cells (SKOV3) secreting IL-21 alone or combination with GM-CSF cytokines was developed and its antitumor effect was evaluated in the nude mice. The gene of IL-21 was amplified from plasmid pRSC-IL-21 by PCR, cloned into the plasmid pRSC-GM-CSF, and the plasmid pRSC-GM-CSF-IL21 was constructed. The plasmids of pRSC-GM-CSF, pRSC-IL21, pRSC-GM-CSF-IL21 and pRSC were respectively transfected into the SKOV3 cells and antitumor efficacy induced by the SKOV3 cells secreting IL-21 or combination with GM-CSF was evaluated by surveying the tumor growth and the nude mice's survival. The results indicated that the secreted IL-21 and GM-CSF were functional because the culture supernatant of SKOV3 cells transfected with the plasmid pRSC-GM-CSF-IL21 enhanced NK cytotoxicity in vitro. The expressions of MIC A/B, NKG2D and ICAM-1 molecules on the SKOV3 cells were up-regulated. The level of IFN-gamma and TNF-alpha, the NK cytotoxicity and the antitumor efficacy were significantly increased in the null mice inoculated with the SKOV3 cells secreting both IL-21 and GM-CSF in comparison with the nude mice inoculated with the other different SKOV3 cells. We concluded that the SKOV3 cells genetically engineered to secrete biologically active IL-21 and GM-CSF elicited antitumor immunity effectively through enhancing NK cytotoxicity, promoting the expressions of MIC A/B, ICAM-1 and NKG2D molecules as well as elevating level of IFN-gamma and TNF-alpha in the nude mice model.

• 出版日期2009-6
• 单位东南大学